The Fragility Index of Hip Arthroscopy Randomized Controlled Trials: A Systematic Survey.
To characterize the fragility index (FI) of statistically significant results from randomized controlled trials (RCTs) in hip arthroscopy. The PubMed-MEDLINE, Embase, and Cochrane databases were queried for hip arthroscopy RCTs published between January 2010 and July 2020. RCTs were included if they contained only 2 treatment arms, randomized patients to a 1:1 allocation to each arm, and reported at least 1 statistically significant dichotomous outcome. The fragility quotient was calculated for each RCT by dividing the FI by the sample size. Smaller FIs indicated more fragile results. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials. We identified 8 hip arthroscopy RCTs that met all inclusion and exclusion criteria. Most of the studies were assessed to have an overall low risk of bias. In the 2 studies with a moderate risk of bias and 1 study with a high risk of bias, concerns were raised about high rates of crossover and loss to follow-up. The median FI was 4, with FIs ranging from 0 to 14, but half of the studies had an FI of 2 or less. In 4 of the 8 studies, the number of patients lost to follow-up was greater than the FI. A systematic survey of hip arthroscopy RCTs resulted in a low FI, indicating that the findings tended to be fragile. A low FI was consistent with findings reported in other orthopaedic and medical literature. Given these results, there is a possibility for findings to be altered by factors such as loss to follow-up, measurement subjectivity, crossover, and biased study design. Results on the fragility of hip arthroscopy RCTs were similar to those reported in general or orthopaedic-specific literature. Level II, systematic review of Level I and II studies.


Effects of colostrum, feeding method and oral IGF1 on porcine uterine development.
Nursing ensures lactocrine delivery of maternally derived, milk-borne bioactive factors to offspring, which affects postnatal development of female reproductive tract tissues. Disruption of lactocrine communication for two days from birth (postnatal day (PND) 0) by feeding milk replacer in lieu of nursing or consumption of colostrum alters porcine uterine gene expression globally by PND 2 and inhibits uterine gland genesis by PND 14. Here, objectives were to determine effects of: (1) nursing or milk replacer feeding from birth; (2) a single dose of colostrum or milk replacer and method of feeding and (3) a single feeding of colostrum or milk replacer, with or without oral supplementation of IGF1, administered at birth on aspects of porcine uterine development at 12-h postnatally. Results indicate nursing for 12 h from birth supports rapid establishment of a uterine developmental program, illustrated by patterns of endometrial cell proliferation, expression of genes associated with uterine wall development and entry into mitosis and establishment of a uterine MMP9/TIMP1 system. A single feeding of colostrum at birth increased endometrial cell proliferation at 12 h, regardless of method of feeding. Oral supplementation of IGF1 was sufficient to support endometrial cell proliferation at 12 h in replacer-fed gilts, and supplementation of colostrum with IGF1 further increased endometrial cell proliferation. Results indicate that lactocrine regulation of postnatal uterine development is initiated with the first ingestion of colostrum. Further, results suggest IGF1 may be lactocrine-active and support a 12-h bioassay, which can be used to identify uterotrophic lactocrine activity.


Climate change and landscape development in post-closure safety assessment of solid radioactive waste disposal: Results of an initiative of the IAEA.
The International Atomic Energy Agency has coordinated an international project addressing climate change and landscape development in post-closure safety assessments of solid radioactive waste disposal. The work has been supported by results of parallel on-going research that has been published in a variety of reports and peer reviewed journal articles. The project is due to be described in detail in a forthcoming IAEA report. Noting the multi-disciplinary nature of post-closure safety assessments, here, an overview of the work is given to provide researchers in the broader fields of radioecology and radiological safety assessment with a review of the work that has been undertaken. It is hoped that such dissemination will support and promote integrated understanding and coherent treatment of climate change and landscape development within an overall assessment process. The key activities undertaken in the project were: identification of the key processes that drive environmental change (mainly those associated with climate and climate change), and description of how a relevant future may develop on a global scale; development of a methodology for characterising environmental change that is valid on a global scale, showing how modelled global changes in climate can be downscaled to provide information that may be needed for characterising environmental change in site-specific assessments, and illustrating different aspects of the methodology in a number of case studies that show the evolution of site characteristics and the implications for the dose assessment models. Overall, the study has shown that quantitative climate and landscape modelling has now developed to the stage that it can be used to define an envelope of climate and landscape change scenarios at specific sites and under specific greenhouse-gas emissions assumptions that is suitable for use in quantitative post-closure performance assessments. These scenarios are not predictions of the future, but are projections based on a well-established understanding of the important processes involved and their impacts on different types of landscape. Such projections support the understanding of, and selection of, plausible ranges of scenarios for use in post-closure safety assessments.


Does a novel penalized likelihood reconstruction of 18F-FDG PET-CT improve signal-to-background in colorectal liver metastases?
Iterative reconstruction algorithms are widely used to reconstruct positron emission tomography computerised tomography (PET/CT) data. Lesion detection in the liver by 18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) is hindered by 18F-FDG uptake in background liver parenchyma. The aim of this study was to compare semi-quantitative parameters of histologically-proven colorectal liver metastases detected by 18F-FDG-PET/CT using data based on a Bayesian penalised likelihood (BPL) reconstruction, with data based on a conventional time-of-flight (ToF) ordered subsets expectation maximisation (OSEM) reconstruction. A BPL reconstruction algorithm was used to retrospectively reconstruct sinogram PET data. This data was compared with OSEM reconstructions. A volume of interest was placed within normal background liver parenchyma. Lesions were segmented using automated thresholding. Lesion maximum standardised uptake value (SUVmax), standard deviation of background liver parenchyma SUV, signal-to-background ratio (SBR), and signal-to-noise ratio (SNR) were collated. Data was analysed using paired Student's t-tests and the Pearson correlation. Forty-two liver metastases from twenty-four patients were included in the analysis. The average lesion SUVmax increased from 8.8 to 11.6 (p<0.001) after application of the BPL algorithm, with no significant difference in background noise. SBR increased from 4.0 to 4.9 (p<0.001) and SNR increased from 10.6 to 13.1 (p<0.001) using BPL. There was a statistically significant negative correlation between lesion size and the percentage increase in lesion SUVmax (p=0.03). This BPL reconstruction algorithm improved SNR and SBR for colorectal liver metastases detected by 18F-FDG-PET/CT, increasing the lesion SUVmax without increasing background liver SUV or image noise. This may improve the detection of FDG-avid focal liver lesions and the diagnostic performance of clinical 18F-FDG-PET/CT in this setting, with the largest impact for small foci.


The significant increase of FcγRIIIA (CD16), a sensitive marker, in patients with coronary heart disease.
Our previous studies suggest that Fc receptor III A of immunoglobulin G (FcγRIIIA, also named CD16) is closely correlated to coronary heart disease (CHD). However, whether or not deregulated FcγRIIIA expression is involved in the development of CHD remains largely unclear. Herein, we investigated the FcγRIIIA mRNA expression in the leukocytes, the serum protein level of soluble CD16 (sCD16) and membrane CD16 on monocytes from 100 diagnosed CHD patients and 40 healthy individuals. Our results demonstrated that there was a significant increase of FcγRIIIA at the mRNA level in leukocytes, and at the protein level for both sCD16 in sera and membrane CD16 on monocytes from CHD patients compared to the healthy control. Similarly to the soluble CD14 (sCD14), the level of macrophage colony stimulating factor (M-CSF) in sera was also higher in CHD patients than that in the control individuals. Furthermore, the levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1), in sera and the mean fluorescent intensity of intercellular adhesion molecule 1 (ICAM-1, CD54) on CD14(+) CD16(+) monocytes were increased in CHD patients. Overall, these data demonstrated that FcγRIIIA (CD16) is involved in the pathogenesis of CHD by activating monocytes and stimulating inflammation. The significant increase of CD14(+) CD16(+) monocytes in CHD patients therefore suggested that the increase of the FcγRIIIA level might be a sensitive marker for the CHD diagnosis.


The subcellular compartmentalization of arginine metabolizing enzymes and their role in endothelial dysfunction.
The endothelial production of nitric oxide (NO) mediates endothelium-dependent vasorelaxation and restrains vascular inflammation, smooth muscle cell proliferation, and platelet aggregation. Impaired production of NO is a hallmark of endothelial dysfunction and promotes the development of cardiovascular disease. In endothelial cells, NO is generated by endothelial nitric oxide synthase (eNOS) through the conversion of its substrate, l-arginine to l-citrulline. Reduced access to l-arginine has been proposed as a major mechanism underlying reduced eNOS activity and NO production in cardiovascular disease. The arginases (Arg1 and Arg2) metabolize l-arginine to generate l-ornithine and urea and increased expression of arginase has been proposed as a mechanism of reduced eNOS activity secondary to the depletion of l-arginine. Indeed, supplemental l-arginine and suppression of arginase activity has been shown to improve endothelium-dependent relaxation and ameliorate cardiovascular disease. However, this simple relationship is complicated by observations that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. Accordingly, the subcellular compartmentalization of intracellular l-arginine into poorly interchangeable pools has been proposed to allow for the local depletion of pools or pockets of l-arginine. In agreement with this, there is considerable evidence supporting the importance of the subcellular localization of l-arginine metabolizing enzymes. In endothelial cells in vitro and in vivo, eNOS is found in discrete intracellular locations and the capacity to generate NO is heavily influenced by its localization inside the cell. Arg1 and Arg2 also reside in different subcellular environments and are thought to differentially influence endothelial function. The plasma membrane solute transporter, CAT-1 and the arginine recycling enzyme, arginosuccinate lyase, co-localize with eNOS and facilitate NO release. Herein, we highlight the importance of the subcellular location of eNOS and arginine transporting and metabolizing enzymes to NO release and cardiovascular disease.


A quantitative survey of Western Muslim attitudes to solid organ donation.
It is imperative for healthcare providers to examine Western Muslim attitudes on organ donation, because they are reluctant donors. We explored such opinion with the aid of a quantitative survey. Voluntary completion of an anonymous survey was promoted (online and paper sampling). For a population target of approximately 1.6 billion, we targeted a completed sample size of 664 to achieve 5% error margins and 99% confidence intervals (assuming 50% response distribution). Logistic regression analysis was performed to assess independent predictors for organ donation approval. In total, 891 global Muslims took the survey with 728 full completions (81.7% completion rate). Paper survey (14% of total) response rate was 62% (124 completed/200 distributed). Western Muslims comprised 76% of participants (n=675) and formed the basis of the analysis. A total of 68.5% of Western Muslims agreed with organ donation, but just 39.3% believed it was compatible with Islam (only 12.7% were registered donors). A total of 1.9% would refuse an organ transplant if required, with 72.4% happy to receive and 25.7% undecided. The main constraints cited by Western Muslims were interpretation of religious scripture (76.5%) and advice from local mosque (70.2%). Predictors for organ donation approval among all global Muslims included younger age, lesser degree of self-rated religiosity, awareness of organ shortages, higher education, and knowing someone with kidney disease/dialysis (all P<0.05). Concern exists among Western Muslims regarding organ donation. Our speculative work should form the basis of larger and more representative assessment of global Muslims to facilitate targeted initiatives to raise awareness.


Fate of the hypertrophic chondrocyte: microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate.
The goal of this review is to examine the fate of the hypertrophic chondrocyte in the epiphyseal growth plate and consider the impact of the cartilage microenvironment on cell survival and apoptosis. Early investigations pointed to a direct role of the hypertrophic chondrocyte in osteogenesis. The terminally differentiated cells were considered to undergo a dramatic change in shape, size, and phenotype, and assume the characteristics of an osteoblast. While some studies have supported the notion of transdifferentiation, much of the evidence in favor of reprogramming epiphyseal chondrocytes is circumstantial and based on microscopic evaluation of cells that are present at the chondro-osseous junction. Although these investigations provided a novel perspective on endochondral bone formation, they were flawed by the failure to consider the importance of stem cells in osseous tissue formation. Subsequent studies indicated that many, if not all, of the cells of the cartilage plate die through the induction of apoptosis. With respect to agents that mediate apoptosis, at the chondro-osseous junction, solubilization of mineral and hydrolysis of organic matrix constituents by septoclasts generates high local concentrations of ions, peptides, and glycans, and secreted matrix metalloproteins. Individually, and in combination, a number of these agents serve as potent chondrocyte apoptogens. We present a new concept: hypertrophic cells die through the induction of autophagy. In the cartilage microenvironment, combinations of local factors cause chondrocytes to express an initial survival phenotype and oxidize their own structural macromolecules to generate ATP. While delaying death, autophagy leads to a state in which cells are further sensitized to changes in the local microenvironment. One such change is similar to ischemia reperfusion injury, a condition that leads to tissue damage and cell death. In the growth cartilage, an immediate effect of this type of injury is sensitization to local apoptogens. These two concepts (type II programmed cell death and ischemia reperfusion injury) emphasize the importance of the local microenvironment, in particular pO(2), in directing chondrocyte survival and apoptosis.


Obesity and the Relative Risk of Knee Replacement Surgery in Patients With Knee Osteoarthritis: A Prospective Cohort Study.
It is unclear what impact obesity has on the progression of knee osteoarthritis (OA) from diagnosis to knee replacement surgery. This study was undertaken to examine the relative risk of knee replacement surgery in overweight and obese patients who were newly diagnosed as having knee OA in a community setting. Subjects were selected from the Information System for Development of Primary Care Research database, which compiles comprehensive clinical information collected by health care professionals for >5.5 million people in Catalonia, Spain (80% of the population). Patients newly diagnosed as having knee OA in primary care between 2006 and 2011 were included. Knee replacement was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification codes from linked hospital admissions data. Multivariable Cox regression models were fitted for knee replacement according to body mass index (BMI), and were adjusted for relevant confounders. Population proportional attributable risk was calculated. A total of 105,189 participants were followed up for a median of 2.6 years (interquartile range 1.3-4.2). Of these patients, 7,512 (7.1%) underwent knee replacement. Adjusted hazard ratios and 95% confidence intervals (95% CIs) for knee replacement for the World Health Organization BMI categories were 1.41 (95% CI 1.27-1.57) for overweight, 1.97 (95% CI 1.78-2.18) for obese I, 2.39 (95% CI 2.15-2.67) for obese II, and 2.67 (95% CI 2.34-3.04) for obese III compared to normal weight. The effect of BMI on risk of knee replacement was stronger among younger participants. The population attributable risk of obesity for knee OA-related knee replacement was 31.0%. Overweight and obese patients are at >40% and 100% increased risk of knee replacement surgery, respectively, compared to patients with normal weight. This association is even stronger in younger patients. Weight reduction strategies could potentially reduce the need for knee replacement surgery by 31% among patients with knee OA.


Survey on Colostrum Management by Dairy Farmers in the Netherlands.
Colostrum feeding is essential for the transfer of passive immunity and health of newborn calves. Information on current colostrum management practices to reduce calf morbidity and mortality is important but lacking for Dutch dairy herds. We therefore conducted a survey to investigate colostrum management strategies on Dutch dairy farms. The survey was specifically focused on the most recently born calf and was returned by 107 respondents (response rate of 13.4%). The mean amount of colostrum fed at first feeding was 2.9 liters. Overall, 79% of farmers provided the calf with at least 6 liters of colostrum in up to three feedings. The majority of respondents (84%) claimed to provide the calf with colostrum for the first time within 2 h post-partum. Using ordinal logistic regression and Wilcoxon rank sum test, we found no differences in time to first colostrum feeding or total amount of colostrum fed between bull calves and heifer calves, respectively. Ordinal logistic regression showed no significant differences in time to first colostrum feeding or time between calving and removing the calf from the dam between AMS and conventional milking herds. Two sample T-test comparing the total volume of colostrum showed no significant difference between AMS and conventional milking herds. Time of day at which a calf was born affected both volume fed at first colostrum feeding and time until first colostrum feeding. Calves born between 00.00 and 06.00 were significantly at risk of receiving the first colostrum later as compared to calves born at other times. Calves born in the evening received on average a lower amount of colostrum at first feeding. Survey results on colostrum management on most Dutch dairy farms are in agreement with the advice to feed as soon as possible after parturition and to provide at least 6 liters within 24 h of age. The current study points at time of calving as a potential risk factor for sub-optimal colostrum feeding. Further research is necessary to determine the consequences of this observation.


Modern conceptions of elite medical practice among internal medicine faculty members.
To understand the modern conceptions of elite practice informing the hidden curriculum through use of peer nominations asking clinicians to identify exceptional practitioners. We distributed a Web-based survey to Department of Medicine faculty at five universities in North America. Participants were asked to nominate individuals they deemed to be "outstanding practitioners" and to provide reasons. They were then asked to nominate "exceptional diagnosticians" and "exceptional professionals." Two hundred eighty-two physicians nominated 558 unique peers as "outstanding practitioners." Justifications included knowledge (45.1%), patient-related interpersonal skill (18.7%), teaching skill (10.8%), and research success (6.8%). More "exceptional diagnostician" nominees were nominated as "outstanding practitioners" (65.2%) relative to "exceptional professional" nominees (56.1%), although the effect size was small (phi = 0.09). Knowledge-based competencies maintain a central role in modern conceptions of elite medical practice, although, contrary to the historical dominance of biomedical abilities, a diverse set of skills and professional aptitudes are also well represented.


Development of INDEL markers to discriminate all genome types rapidly in the genus Oryza.
The wild Oryza species are rich in genetic diversity and are good resources for modern breeding of rice varieties. The reliable ex situ conservation of various genetic resources supports both basic and applied rice research. For this purpose, we developed PCR-based and co-dominant insertion/deletion (INDEL) markers which enable the discrimination of the genome types or species in the genus Oryza. First, 12,107 INDEL candidate sequences were found in the BAC end sequences for 12 Oryza species available in public databases. Next, we designed PCR primers for INDEL-flanking sequences to match the characteristics of each INDEL, based on an assessment of their likelihood to give rise to a single or few PCR products in all 102 wild accessions, covering most Oryza genome types. Then, we selected 22 INDEL markers to discriminate all genome types in the genus Oryza. A phylogenetic tree of 102 wild accessions and two cultivars according to amplicon polymorphisms for the 22 INDEL markers corresponded well to those in previous studies, indicating that the INDEL markers developed in this study were a useful tool to improve the reliability of identification of wild Oryza species in the germplasm stocks.


Providing Informal Care in Terminal Illness: An Analysis of Preferences for Support Using a Discrete Choice Experiment.
The trend for terminally ill patients to receive much of their end-of-life care at home necessitates the design of services to facilitate this. Care at home also requires that informal care be provided by family members and friends. This study investigated informal carers' preferences for support services to aid the development of end-of-life health care services. This cross-sectional study used 2 discrete choice experiments to ascertain the preferences of carers supporting patients with different levels of care need, determined by the assistance needed with personal care and labeled High Care (HC) and Low Care (LC). The sample included 168 informal carers of people receiving palliative care at home from 2 palliative care services in Sydney, Australia. Data were collected in face-to-face interviews; carers chose between 2 hypothetical plans of support services and their current services. Data were analyzed with generalized multinomial logit models that were used to calculate the impact of each attribute on the probability of a carer choosing a service plan. Preferred support included nursing services; the probability of choosing a plan increased significantly if it included nurse home visits and phone advice (P < 0.001). HC carers also wanted doctor home visits, home respite, and help with personal care (P < 0.05), and LC carers wanted help with household tasks, transport, and a case coordinator (P < 0.001). On average, both groups of carers preferred their current services, but this varied with characteristics of the carer and the caregiving situation. The most valued services are those that support carers in their caregiving role; however, supportive care preferences vary with the different circumstances of patients and carers.


Racial disparities in utilization of specialist care and medications in inflammatory bowel disease.
Optimization of medical therapy and specialist care for inflammatory bowel disease (IBD) may reduce morbidity. We sought to characterize racial disparities in utilization of healthcare and medical therapy for IBD. We performed a cross-sectional study of black (n=137) and white (n=149) IBD patients recruited from an outpatient IBD clinic and through medical record review and telephone interview, compared utilization of IBD specialist services, emergency department (ED) services, and medications. We adjusted racial comparisons for demographic, socioeconomic, and clinical factors. After adjustment for confounders, blacks were less likely than whites to be under the regular care (defined as at least annual visit) of a gastroenterologist (adjusted odds ratio (aOR) 0.43; 95% confidence interval (CI): 0.25-0.75) or IBD specialist (aOR 0.37; 95% CI: 0.22-0.61). Follow-up with a primary care provider was, however, similar between blacks and whites. Over the preceding 12 months, blacks were more likely than whites to have at least one visit to the ED (aOR 2.02; 95% CI: 1.22-3.35), but there was no difference in hospitalization. Among CD patients with prolonged steroid use, blacks were less likely than whites to have been on infliximab (aOR 0.41; 95% CI: 0.21-0.77), but there were no racial differences in the use of immunomodulators (aOR 0.87; 95% CI: 0.48-1.60). There are racial differences in utilization of IBD-related specialist services, ED visits, and infliximab that are independent of income and education. Modifiable barriers to health-care access may have a role in these disparities.


The genome of the Gram-positive metal- and sulfate-reducing bacterium Desulfotomaculum reducens strain MI-1.
Spore-forming, Gram-positive sulfate-reducing bacteria (SRB) represent a group of SRB that dominates the deep subsurface as well as niches in which resistance to oxygen and dessication is an advantage. Desulfotomaculum reducens strain MI-1 is one of the few cultured representatives of that group with a complete genome sequence available. The metabolic versatility of this organism is reflected in the presence of genes encoding for the oxidation of various electron donors, including three- and four-carbon fatty acids and alcohols. Synteny in genes involved in sulfate reduction across all four sequenced Gram-positive SRB suggests a distinct sulfate-reduction mechanism for this group of bacteria. Based on the genomic information obtained for sulfate reduction in D. reducens, the transfer of electrons to the sulfite and APS reductases is proposed to take place via the quinone pool and heterodisulfide reductases respectively. In addition, both H(2) -evolving and H(2) -consuming cytoplasmic hydrogenases were identified in the genome, pointing to potential cytoplasmic H(2) cycling in the bacterium. The mechanism of metal reduction remains unknown.


Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia.
Similar vascular pathological conditions are observed in diabetic animals and those with diet-induced hypergalactosemia. Both diabetes and hypergalactosemia are believed to cause vascular dysfunction via a common biochemical mechanism. In this study, we have found that both diabetes and hypergalactosemia in the short term (2-4 months) can increase total diacylglycerol (DAG) levels by 52 +/- 9 and 74 +/- 13% in the retina and aorta, respectively, of diabetic dogs, and by 94 +/- 9 and 78 +/- 11% in the retina and aorta, respectively, in dogs with hypergalactosemia as compared with normal control animals (P < 0.01). The elevation of DAG levels was maintained for 5 years in the aortas of diabetic and hypergalactosemic dogs. To characterize the mechanism of the DAG increases, we have determined that total DAG levels were significantly increased in cultured macro- and microvascular cells exposed to elevated glucose (22 mM) and galactose (16.5 mM) levels. These increased levels were not prevented by sorbinil, an aldose reductase inhibitor. One of the sources of the increased DAG levels was probably derived from de novo synthesis from both hexoses as determined by radiolabeling studies. Intracellularly, the DAG elevation activated protein kinase C (PKC) activity with increases of 58 +/- 12% (P < 0.05) and 66 +/- 8% (P < 0.01) in the membrane fraction of cultured aortic smooth muscle cells exposed to elevated glucose and galactose levels, respectively. These findings have clearly demonstrated a possible common biochemical mechanism by which hyperglycemia and hypergalactosemia can chronically activate the DAG-PKC pathway in the vasculature and could be a possible explanation for the development of diabetic vascular complications.


Coccidial infections of goats in Selangor, peninsular Malaysia.
Coccidial infections were studied in goats in the state of Selangor (peninsular Malaysia) during a 12-month period. The study included 10 smallholder farms on which kids were monitored for faecal oocyst counts from birth until 1-year old. Eimeria oocysts were found in 725 (89%) of 815 faecal samples examined. Nine species of Eimeria were identified. The most prevalent were E. arloingi, found in 71% of the samples, E. ninakohlyakimovae (67%), E. christenseni (63%) and E. alijevi (61%). The other species found were, E. hirci, E. jolchijevi, E. caprovina, E. caprina and E. pallida, present in 34, 22, 12, 9 and 4% of the samples, respectively. Oocyst counts were significantly higher in animals of less than 4-months old (P < 0.05). High oocyst counts were mainly caused by non-pathogenic species. Poor hygienic conditions were found to be associated with a higher intensity of coccidial infections. Mortality rates in kids could not be related to the intensity of coccidial infections.


CloudSat 2C-ICE product update with a new Ze parameterization in lidar-only region.
The CloudSat 2C-ICE data product is derived from a synergetic ice cloud retrieval algorithm that takes as input a combination of CloudSat radar reflectivity (Ze ) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation lidar attenuated backscatter profiles. The algorithm uses a variational method for retrieving profiles of visible extinction coefficient, ice water content, and ice particle effective radius in ice or mixed-phase clouds. Because of the nature of the measurements and to maintain consistency in the algorithm numerics, we choose to parameterize (with appropriately large specification of uncertainty) Ze and lidar attenuated backscatter in the regions of a cirrus layer where only the lidar provides data and where only the radar provides data, respectively. To improve the Ze parameterization in the lidar-only region, the relations among Ze , extinction, and temperature have been more thoroughly investigated using Atmospheric Radiation Measurement long-term millimeter cloud radar and Raman lidar measurements. This Ze parameterization provides a first-order estimation of Ze as a function extinction and temperature in the lidar-only regions of cirrus layers. The effects of this new parameterization have been evaluated for consistency using radiation closure methods where the radiative fluxes derived from retrieved cirrus profiles compare favorably with Clouds and the Earth's Radiant Energy System measurements. Results will be made publicly available for the entire CloudSat record (since 2006) in the most recent product release known as R05.


Streptococcus pneumoniae: transmission, colonization and invasion.
Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.


Increased markers of oxidative stress in plasma of patients with chronic pancreatitis.
Chronic pancreatitis (CP) is a heterogeneous disease defined as chronic inflammatory changes of the pancreatic tissue caused by variety of aetiologies. Oxidative stress accompanying the inflammatory processes has been suggested as an important factor contributing to CP development. The aim of this study was to determine levels of lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), together with nitrites and the total antioxidant capacity in the plasma of patients with CP and control subjects. One hundred and five patients with chronic pancreatitis and twenty seven healthy controls were included into this study. Levels of MDA and 4-HNE were analyzed using high-performance liquid chromatography. The total antioxidant capacity of plasma against peroxyl radicals was evaluated using chemiluminescent determination. Nitrites were determined using Griess reaction. Biochemical and haematological parameters were measured by standard methods. The plasma levels of both MDA and 4-HNE, together with the plasma levels of nitrites, were significantly higher in CP patients, compared to healthy controls. The total antioxidant capacity did not differ significantly. Biochemical parameters were in the normal range. The MDA and 4-HNE levels correlated positively with the levels of high-density lipoprotein cholesterol. Nitrite levels correlated positively with C-reactive protein, total white blood cells, and triglycerides. The significantly increased plasma levels of MDA, 4-HNE, and nitrites indicate that oxidative stress is present in patients with CP and that it may play a role in initiation and maintenance of inflammation within the pancreatic tissue in CP patients.


Brain, blood, and iron: perspectives on the roles of erythrocytes and iron in neurodegeneration.
The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly rare and challenging to study. The NBIA disorders are defined by their appearance on brain magnetic resonance imaging, with iron deposition in the basal ganglia. Clinical features vary, but most include a movement disorder. New causative genes are being rapidly identified; however, the mechanisms by which mutations cause iron accumulation and neurodegeneration are not well understood. NA syndromes are also characterized by a progressive movement disorder, accompanied by cognitive and psychiatric features, resulting from mutations in a number of genes whose roles are also basically unknown. An overlapping feature of the two groups, NBIA and NA, is the occurrence of acanthocytes, spiky red cells with a poorly-understood membrane dysfunction. In this review we summarise recent developments in this field, specifically insights into cellular mechanisms and from animal models. Cell membrane research may shed light upon the significance of the erythrocyte abnormality, and upon possible connections between the two sets of disorders. Shared pathophysiologic mechanisms may lead to progress in the understanding of other types of neurodegeneration.


Absence of an association between glucose levels and surgical site infections in patients undergoing craniotomies for brain tumors.
In select patient populations, hyperglycemia has been shown to increase the risk of surgical site infection (SSI), whereas stringent glucose control has improved outcomes. To date, no study has focused on whether SSIs in patients with brain tumors undergoing resection are associated with hyperglycemia. The authors performed a retrospective chart review of patients who underwent a craniotomy after receiving a diagnosis of brain tumor. From 2001 to 2008, 2485 patients underwent a craniotomy for tumor resection at the Brain Tumor & Neuro-Oncology Center at the Cleveland Clinic. Fifty-seven of these patients (2.3%) developed SSIs postoperatively. A matched case-control study design was used, with 57 patients who developed SSIs after craniotomy (cases) matched with 57 patients who did not develop SSIs (controls). The results were analyzed using both univariate and multivariate conditional logistic regression. Glucose level was not a significant factor in postoperative SSI (p = 0.83) after adjusting for duration of surgery and adherence to antibiotic prophylaxis. However, duration of surgery was significantly associated with postoperative SSI (p = 0.047). For patients who undergo craniotomy for definitive resection of a brain tumor, duration of surgery described more variation in the model to predict SSI than blood glucose levels.


Vertebral body stenting versus kyphoplasty for the treatment of osteoporotic vertebral compression fractures: a randomized trial.
In the treatment of vertebral compression fractures, vertebral body stenting with an expandable scaffold inserted before application of the bone cement was developed to impede secondary loss of vertebral height encountered in patients treated with balloon kyphoplasty. The purpose of this study was to clarify whether there are relevant differences between balloon kyphoplasty and vertebral body stenting with regard to perioperative and postoperative findings. In a two-armed randomized controlled trial, patients with a total of 100 fresh osteoporotic vertebral compression fractures were treated with either balloon kyphoplasty or vertebral body stenting. The primary outcome was the post-interventional change in the kyphotic angle on radiographs. The secondary outcomes were the maximum pressure of the balloon tamp during inflation, radiation exposure time, perioperative complications, and cement leakage. The mean reduction (and standard deviation) of kyphosis (the kyphotic correction angle) was 4.5° ± 3.6° after balloon kyphoplasty and 4.7° ± 4.2° after vertebral body stenting (p = 0.972). The mean pressures were 24 ± 5 bar (348 ± 72 pounds per square inch [psi]) during vertebral body stenting and 16 ± 6 bar (233 ± 81 psi) during balloon kyphoplasty (p = 0.014). There were no significant differences in radiation exposure time.None of the patients underwent revision surgery, and postoperative neurologic sequelae were not observed. Cement leakage occurred at twenty-five of the 100 vertebral levels without significant differences between the two intervention arms (p = 0.230). Intraoperative material-related complications were observed at one of the fifty vertebral levels in the balloon kyphoplasty group and at nine of the fifty levels in the vertebral body stenting group. No beneficial effect of vertebral body stenting over balloon kyphoplasty was found among patients with painful osteoporotic vertebral fractures with regard to kyphotic correction, cement leakage, radiation exposure time, or neurologic sequelae. Vertebral body stenting was associated with significantly higher pressures during balloon inflation and more material-related complications.


Evaluation of computer generated neonatal discharge summaries.
Computer generated and dictated discharge summaries were compared for all 133 babies admitted for intensive and special care during a six month period. Whereas 130/133 (98%) had a computer generated summary, only 94/133 (71%) had a dictated summary. In addition, computerised summaries were completed at discharge, but there was a delay up to 26 weeks for dictated summaries. Dictated summaries had more items of basic data missing but were more readable. A main diagnosis was missing in only 5/95 (5%) of dictated and 1/130 (1%) computerised summaries. Of the computer generated summaries, 114/133 (86%) were suitable to give to parents. Satisfactory discharge summaries for babies requiring intensive or special care can be generated with an on line computer system.


Band structure engineering via piezoelectric fields in strained anisotropic CdSe/CdS nanocrystals.
Strain in colloidal heteronanocrystals with non-centrosymmetric lattices presents a unique opportunity for controlling optoelectronic properties and adds a new degree of freedom to existing wavefunction engineering and doping paradigms. We synthesized wurtzite CdSe nanorods embedded in a thick CdS shell, hereby exploiting the large lattice mismatch between the two domains to generate a compressive strain of the CdSe core and a strong piezoelectric potential along its c-axis. Efficient charge separation results in an indirect ground-state transition with a lifetime of several microseconds, almost one order of magnitude longer than any other CdSe/CdS nanocrystal. Higher excited states recombine radiatively in the nanosecond time range, due to increasingly overlapping excited-state orbitals. k˙p calculations confirm the importance of the anisotropic shape and crystal structure in the buildup of the piezoelectric potential. Strain engineering thus presents an efficient approach to highly tunable single- and multiexciton interactions, driven by a dedicated core/shell nanocrystal design.


Alpha1E-containing Ca2+ channels are involved in synaptic plasticity.
Long-term potentiation (LTP) is the most prominent model for the molecular and cellular mechanisms of learning and memory. Two main forms of LTP have been distinguished. The N-methyl-D-aspartate-receptor-dependent forms of LTP have been studied most extensively, whereas much less is known about N-methyl-D-aspartate-receptor-independent forms of LTP. This latter type of LTP was first described at the mossy fiber synapses in the hippocampus and subsequently at parallel fiber synapses in the cerebellum as well as at corticothalamic synapses. These presynaptic forms of LTP require a rise in the intraterminal calcium concentration, but the channel through which calcium passes has not been identified. By using pharmacological tools as well as genetic deletion, we demonstrate here that alpha1E-containing voltage-dependent calcium channels (VDCCs) shift the threshold for mossy fiber LTP. The channel is not involved in the expression mechanism, but it contributes to the calcium influx during the induction phase. Indeed, optical recordings directly show the presence and the function of alpha1E-containing VDCCs at mossy fiber terminals. Hence, a previously undescribed role for alpha1E-containing VDCCs is suggested by these results.


Cytoplasmic RNA quality control failure engages mTORC1-mediated autoinflammatory disease.
Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. The SKIV2L RNA exosome is cytoplasmic RNA degradation machinery that was thought to be essential for preventing the self-RNA-mediated interferon (IFN) response. Here, we demonstrate the physiological function of SKIV2L in mammals. We found that Skiv2l deficiency in mice disrupted epidermal and T cell homeostasis in a cell-intrinsic manner independently of IFN. Skiv2l-deficient mice developed skin inflammation and hair abnormality, which were also observed in a SKIV2L-deficient patient. Epidermis-specific deletion of Skiv2l caused hyperproliferation of keratinocytes and disrupted epidermal stratification, leading to impaired skin barrier with no appreciable IFN activation. Moreover, Skiv2l-deficient T cells were chronically hyperactivated and these T cells attacked lesional skin as well as hair follicles. Mechanistically, SKIV2L loss activated the mTORC1 pathway in both keratinocytes and T cells. Both systemic and topical rapamycin treatment of Skiv2l-deficient mice ameliorated epidermal hyperplasia and skin inflammation. Together, we demonstrate that mTORC1, a classical nutrient sensor, also senses cytoplasmic RNA quality control failure and drives autoinflammatory disease. We also propose SKIV2L-associated trichohepatoenteric syndrome (THES) as a new mTORopathy for which sirolimus may be a promising therapy.


Near-field radiative heat transfer between metamaterial thin films.
We investigate near-field radiative heat transfer between two thin films made of metamaterials. The impact of film thickness on magnetic and electric surface polaritons (ESPs) is analyzed. It is found that the strength as well as the location of magnetic resonance does not change with film thickness until the film behaves as semi-infinite for the dielectric function chosen in this study. When the film is thinner than vacuum gap, both electric and magnetic polaritons contribute evenly to near-field radiative heat transfer. At larger film thicknesses, ESPs dominate heat transfer due to excitation of a larger number of modes. Results obtained from this study will facilitate applications of metamaterials as thin-film coatings for energy systems.


Neurogenin 3 is regulated by neurotrophic tyrosine kinase receptor type 2 (TRKB) signaling in the adult human exocrine pancreas.
Reports of exocrine-to-endocrine reprogramming through expression or stabilization of the transcription factor neurogenin 3 (NGN3) have generated renewed interest in harnessing pancreatic plasticity for therapeutic applications. NGN3 is expressed by a population of endocrine progenitor cells that give rise exclusively to hormone-secreting cells within pancreatic islets and is necessary and sufficient for endocrine differentiation during development. In the adult human pancreas, NGN3 is expressed by dedifferentiating exocrine cells with a phenotype resembling endocrine progenitor cells and the capacity for endocrine differentiation in vitro. Neurotrophic tyrosine kinase receptor type 2 (TRKB), which regulates neuronal cell survival, differentiation and plasticity, was identified as highly overexpressed in the NGN3 positive cell transcriptome compared to NGN3 negative exocrine cells. This study was designed to determine if NGN3 is regulated by TRKB signaling in the adult human exocrine pancreas. Transcriptome analysis, quantitative reverse transcriptase polymerase chain reaction (RTPCR) and immunochemistry were used to identify TRKB isoform expression in primary cultures of human islet-depleted exocrine tissue and human cadaveric pancreas biopsies. The effects of pharmacological modulation of TRKB signaling on the expression of NGN3 were assessed by Student's t-test and ANOVA. Approximately 30 % of cultured exocrine cells and 95 % of NGN3+ cells express TRKB on their cell surface. Transcriptome-based exon splicing analyses, isoform-specific quantitative RTPCR and immunochemical staining demonstrate that TRKB-T1, which lacks a tyrosine kinase domain, is the predominant isoform expressed in cultured exocrine tissue and is expressed in histologically normal cadaveric pancreas biopsies. Pharmacological inhibition of TRKB significantly decreased the percentage of NGN3+ cells, while a TRKB agonist significantly increased this percentage. Inhibition of protein kinase B (AKT) blocked the effect of the TRKB agonist, while inhibition of tyrosine kinase had no effect. Modulation of TRKB and AKT signaling did not significantly affect the level of NGN3 mRNA. In the adult human exocrine pancreas, TRKB-T1 positively regulates NGN3 independent of effects on NGN3 transcription. Targeting mechanisms controlling the NGN3+ cell population size and endocrine cell fate commitment represent a potential new approach to understand pancreas pathobiology and means whereby cell populations could be expanded for therapeutic purposes.


Muscle Performance Changes with Age in Active Women.
The purpose of this study was to examine age-related differences in muscle performance in women divided into young (YW, 20-39 years, n = 29) middle-aged (MAW, 40-59 years, n = 33), and older (OW, ≥60 years, n = 40) age groups. Hand grip strength, vertical jump performance, and knee extensor (KE) strength (0 deg/s, 60 deg/s, and 240 deg/s), speed of movement (SoM; at 1 Nm, 20%, 40%, and 60% isometric strength), and endurance (30-repetition test at 60 degs/s and 240 deg/s) were assessed. Computed tomography-acquired muscle cross-sectional area (mCSA) was measured and included to determine specific strength (KE strength/mCSA). Hand grip strength was similar across groups, while jump performance declined with age (YW and MAW > OW, p < 0.001). KE strength declined significantly with age (all conditions p < 0.01), while specific strength was similar across groups. SoM was significantly higher for YW and MAW compared to OW (both p < 0.01). An age × velocity interaction revealed YW KE endurance was similar between conditions, whereas MAW and OW displayed significantly better endurance during the 60 deg/s condition. OW displayed impaired KE endurance at 240 deg/s (vs. YW and MAW, p < 0.01) but improved at 60 deg/s (vs. YW, p < 0.01). Dynamic torque decline increased with age (YW < OW, p = 0.03) and was associated with intramuscular adipose tissue (r = 0.21, p = 0.04). Performance declines were most evident among OW, but few performance deficits had emerged in MAW. Interestingly, strength declines disappeared after normalizing to mCSA and endurance appears to be velocity-dependent.


Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment.
Lafora disease (LD), an autosomal recessive neurodegenerative disorder, is characterized by the presence of cytoplasmic polyglucosan inclusions known as Lafora bodies in several tissues including the brain. Laforin, a protein phosphatase, and malin, an ubiquitin ligase, are two of the proteins that are known to be defective in LD. Malin interacts with laforin and promotes its polyubiquitination and degradation. Here we show that malin and laforin co-localize in endoplasmic reticulum (ER) and that they form centrosomal aggregates when treated with proteasomal inhibitors in both neuronal and non-neuronal cells. Laforin/malin aggregates co-localize with gamma-tubulin and cause redistribution of alpha-tubulin. These aggregates are also immunoreactive to ubiquitin, ubiquitin-conjugating enzyme, ER chaperone and proteasome subunits, demonstrating their aggresome-like properties. Furthermore, we show that the centrosomal aggregation of laforin and malin is dependent on the functional microtubule network. Laforin and malin form aggresome when expressed together or otherwise, suggesting that the two proteins are recruited to the centrosome independent of each other. Taken together, our results suggest that the centrosomal accumulation of malin, possibly with the help of laforin, may enhance the ubiquitination of its substrates and facilitate their efficient degradation by proteasome. Defects in malin or laforin may thus lead to increased levels of misfolded and/or target proteins, which may eventually affect the physiological processes of the neuron. Thus, defects in protein degradation and clearance are likely to be the primary trigger in the physiopathology of LD.


Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever.
Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance.


Differential effects of the APOE genotype on brain function across the lifespan.
Increasing age and carrying an APOE ε4 allele are well established risk factors for Alzheimer's disease (AD). The earlier age of onset of AD observed in ε4-carriers may reflect an accelerated aging process. We recently reported that APOE genotype modulates brain function decades before the appearance of any cognitive or clinical symptoms. Here we test the hypothesis that APOE influences brain aging by comparing healthy ε4-carriers and non-carriers, using the same imaging protocol in distinct groups of younger and older healthy volunteers. A cross-sectional factorial design was used to examine the effects of age and APOE genotype, and their interaction, on fMRI activation during an encoding memory task. The younger (N=36; age range 20-35; 18 ε4-carriers) and older (35 middle-age/elderly; age range 50-78 years; 15 ε4-carriers) healthy volunteers taking part in the study were cognitively normal. We found a significant interaction between age and ε4-status in the hippocampi, frontal pole, subcortical nuclei, middle temporal gyri and cerebellum, such that aging was associated with decreased activity in e4-carriers and increased activity in non-carriers. Reduced cerebral blood flow was found in the older ε4-carriers relative to older non-carriers despite preserved grey matter volume. Overactivity of brain function in young ε4-carriers is disproportionately reduced with advancing age even before the onset of measurable memory impairment. The APOE genotype determines age-related changes in brain function that may reflect the increased vulnerability of ε4-carriers to late-life pathology or cognitive decline.


Health Policy for Dialysis Care in Canada and the United States.
Contemporary dialysis treatment for chronic kidney failure is complex, is associated with poor clinical outcomes, and leads to high health costs, all of which pose substantial policy challenges. Despite similar policy goals and universal access for their kidney failure programs, the United States and Canada have taken very different approaches to dealing with these challenges. While US dialysis care is primarily government funded and delivered predominantly by private for-profit providers, Canadian dialysis care is also government funded but delivered almost exclusively in public facilities. Differences also exist for regulatory mechanisms and the policy incentives that may influence the behavior of providers and facilities. These differences in health policy are associated with significant variation in clinical outcomes: mortality among patients on dialysis is consistently lower in Canada than in the United States, although the gap has narrowed in recent years. The observed heterogeneity in policy and outcomes offers important potential opportunities for each health system to learn from the other. This article compares and contrasts transnational dialysis-related health policies, focusing on key levers including payment, finance, regulation, and organization. We also describe how policy levers can incentivize favorable practice patterns to support high-quality/high-value, person-centered care and to catalyze the emergence of transformative technologies for alternative kidney replacement strategies.


Childhood sexual abuse and the sociocultural context of sexual risk among adult Latino gay and bisexual men.
We sought to examine the relationships among childhood sexual abuse, social discrimination, psychological distress, and HIV-risk among Latino gay and bisexual men in the United States. Data were from a probability sample of 912 men from Miami, FL; Los Angeles, CA; and New York, NY. We used logistic regression and path analyses to examine direct and indirect effects of childhood sexual abuse on psychological distress and sexual risk behavior. We found a 15.8% (95% confidence interval = 12.3%, 19.2%) prevalence of childhood sexual abuse. Not having sex before age 16 years and having consensual sex before age 16 years did not differ from each other in predicting any of the outcomes of interest. Forced sex was associated with a significantly increased risk for all outcomes. A path analyses yielded direct effects of childhood sexual abuse and exposure to homophobia during childhood and during adulthood on psychological distress and indirect effects on risky sexual behavior. HIV-risk patterns among Latino gay and bisexual men are related to childhood sexual abuse and a social context of discrimination, which combined lead to symptoms of psychological distress and participation in risky sexual situations that increase risky sexual behaviors associated with HIV acquisition.


Genome-wide screen of ovary-specific DNA methylation in polycystic ovary syndrome.
To compare genome-wide DNA methylation profiles in ovary tissue from women with polycystic ovary syndrome (PCOS) and healthy controls. Case-control study matched for age and body mass index. University-affiliated hospital. Ten women with PCOS who underwent ovarian drilling to induce ovulation and 10 healthy women who were undergoing laparoscopic sterilization, hysterectomy for benign conditions, diagnostic laparoscopy for pelvic pain, or oophorectomy for nonovarian indications. None. Genome-wide DNA methylation patterns determined by immunoprecipitation and microarray (MeDIP-chip) analysis. The methylation levels were statistically significantly higher in CpG island shores (CGI shores), which lie outside of core promoter regions, and lower within gene bodies in women with PCOS relative to the controls. In addition, high CpG content promoters were the most frequently hypermethylated promoters in PCOS ovaries but were more often hypomethylated in controls. Second, 872 CGIs, specifically methylated in PCOS, represented 342 genes that could be associated with various molecular functions, including protein binding, hormone activity, and transcription regulator activity. Finally, methylation differences were validated in seven genes by methylation-specific polymerase chain reaction. These genes correlated to several functional families related to the pathogenesis of PCOS and may be potential biomarkers for this disease. Our results demonstrated that epigenetic modification differs between PCOS and normal ovaries, which may help to further understand the pathophysiology of this disease.


Grain yield trade-offs in spike-branching wheat can be mitigated by elite alleles affecting sink capacity and post-anthesis source activity.
Introducing variations in inflorescence architecture, such as the 'Miracle-Wheat' (Triticum turgidum convar. compositum (L.f.) Filat.) with a branching spike, has relevance for enhancing wheat grain yield. However, in the spike-branching genotypes, the increase in spikelet number is generally not translated into grain yield advantage because of reduced grains per spikelet and grain weight. Here, we investigated if such trade-offs might be a function of source-sink strength by using 385 RILs developed by intercrossing the spike-branching landrace TRI 984 and CIRNO C2008, an elite durum (T. durum L.) cultivar; they were genotyped using the 25K array. Various plant and spike architectural traits, including flag leaf, peduncle and spike senescence rate, were phenotyped under field conditions for two consecutive years. On Chr 5AL, we found a new modifier QTL for spike-branching, branched head t 3 (bh t-A3), which was epistatic to the previously known bh t-A1 locus. Besides, bh t-A3 was associated with more grains per spikelet and a delay in flag leaf senescence rate. Importantly, favourable alleles viz., bh t-A3 and grain protein content (gpc-B1) that delayed senescence are required to improve grain number and grain weight in the spike-branching RILs. In summary, achieving a balanced source-sink relationship might minimise grain yield trade-offs in Miracle-Wheat.


Lidar extinction-to-backscatter ratio of the ocean.
Bio-optical models are used to develop a model of the lidar extinction-to-backscatter ratio applicable to oceanographic lidar. The model is based on chlorophyll concentration, and is expected to be valid for Case 1 waters. The limiting cases of narrow- and wide-beam lidars are presented and compared with estimates based on in situ optical measurements. Lidar measurements are also compared with the model using in situ or satellite estimates of chlorophyll concentration. A modified lidar ratio is defined, in which the properties of pure sea water are removed. This modified ratio is shown to be nearly constant for wide-beam lidar operating in low-chlorophyll waters, so accurate inversion to derive extinction and backscattering is possible under these conditions. This ratio can also be used for lidar calibration.


Molecular genetics of cell interactions in Arabidopsis.
Many events in plant development are regulated by the interactions of neighboring cells. We are interested in determining what sorts of molecules act as signals and/or receptors in these interactions and how these mechanisms relate to those used in animals and fungi. We are presently working on two different types of systems to try to address this question. In one case we are starting at the molecular level and characterizing a family of receptor protein kinase genes which seem natural candidates for mediating cellular interactions. By analyzing the expression patterns of these genes as well as the phenotypes of transgenic plants bearing altered genes we hope to determine what roles these proteins play in plant development. In the second case we are starting from the organismic level and using genetics to identify genes essential to a whole range of cellular interactions which are required for proper male gametophyte development during reproduction. These interactions involve both recognition of the pollen grain to verify that it is from the correct species and also a transfer of positional information from the female to the male which first allows the pollen tube to determine the polarity of the stigmatic cell on which it has germinated and later provides 'guidance' for the elongating tube to find the ovule.


Antihistamine medication may alleviate negative effects of prenatal exposure to polycyclic aromatic hydrocarbons (PAH) on lung function in children. Birth cohort prospective study.
The main purpose of the present study was to test the hypothesis that the depressed lung growth attributable to prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may be modified by the intake of antihistamine medications. Individual prenatal PAH exposure was assessed by personal air monitoring in 176 children who were followed over nine years, in the course of which outdoor residential air monitoring, allergic skin tests for indoor allergens, lung function tests (FVC, FEV(1), FEV(05), and FEF(25-75)) were performed. The analysis with the General Estimated Equation (GEE) showed no association between prenatal PAH exposure and lung function in the group of children who were reported to be antihistamine users. However, in the group of antihistamine non-users all lung function tests except for FEF(25-75) were significantly and inversely associated with prenatal airborne PAH exposure. The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting from PAH exposure may be caused by the allergic inflammation within lung.


Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins.
The emergence of new sequencing technologies has facilitated the use of bacterial whole genome alignments for evolutionary studies and outbreak analyses. These datasets, of increasing size, often include examples of multiple different mechanisms of horizontal sequence transfer resulting in substantial alterations to prokaryotic chromosomes. The impact of these processes demands rapid and flexible approaches able to account for recombination when reconstructing isolates' recent diversification. Gubbins is an iterative algorithm that uses spatial scanning statistics to identify loci containing elevated densities of base substitutions suggestive of horizontal sequence transfer while concurrently constructing a maximum likelihood phylogeny based on the putative point mutations outside these regions of high sequence diversity. Simulations demonstrate the algorithm generates highly accurate reconstructions under realistically parameterized models of bacterial evolution, and achieves convergence in only a few hours on alignments of hundreds of bacterial genome sequences. Gubbins is appropriate for reconstructing the recent evolutionary history of a variety of haploid genotype alignments, as it makes no assumptions about the underlying mechanism of recombination. The software is freely available for download at github.com/sanger-pathogens/Gubbins, implemented in Python and C and supported on Linux and Mac OS X.


Modeling the long-term cost-effectiveness of the caries management system in an Australian population.
The Monitor Practice Program demonstrated that regular monitoring and noninvasive management of dental caries is effective in reducing the incremental DMFT (decayed, missing, and filled teeth) in patients, within the construct of a 3-year randomized clinical trial. This analysis evaluates the long-term cost-effectiveness of the preventive approach underpinning the Caries Management System, used in the general practice setting and modeled to the Australian population. An individual patient-simulation Markov model was developed to compare the long-term costs and outcomes of the Caries Management System versus standard dental care in a hypothetical sample representative of the Australian population. Eight Markov submodels were developed, representing eight molar teeth (excluding wisdom teeth), each consisting of 11 health states simulating the incidence and progression of dental caries, and future interventions such as fillings and crowns. Transition probabilities and costs assigned to health states were based on claims data from the second largest private health insurer in Australia. The economic evaluation was performed from the Australian private dental practitioner perspective. The incremental cost per DMFT avoided was calculated at three time points: 2 years, 3 years, and lifetime. Univariate sensitivity analysis was conducted to test the robustness of the results. The incremental cost per DMFT avoided at 2 years, 3 years, and lifetime was estimated to be $1287.07, $1148.91, and $1795.06, respectively. The analysis suggests that the Caries Management System is most cost-effective in patients with a high risk of dental caries.


Wolbachia transinfections in Culex quinquefasciatus generate cytoplasmic incompatibility.
Culex quinquefasciatus is an important mosquito vector of a number of viral and protozoan pathogens of humans and animals, and naturally carries the endosymbiont Wolbachia pipientis, strain wPip. Wolbachia are used in two distinct vector control strategies: firstly, population suppression caused by mating incompatibilities between mass-released transinfected males and wild females; and secondly, the spread of pathogen transmission-blocking strains through populations. Using embryonic microinjection, two novel Wolbachia transinfections were generated in C. quinquefasciatus using strains native to the mosquito Aedes albopictus: a wAlbB single infection, and a wPip plus wAlbA superinfection. The wAlbB infection showed full bidirectional cytoplasmic incompatibility (CI) with wild-type C. quinquefasciatus in reciprocal crosses. The wPipwAlbA superinfection showed complete unidirectional CI, and therefore population invasion potential. Whereas the wAlbB strain showed comparatively low overall densities, similar to the native wPip, the wPipwAlbA superinfection reached over 400-fold higher densities in the salivary glands compared to the native wPip, suggesting it may be a candidate for pathogen transmission blocking.


Direct Comparison of Wharton's Jelly and Bone Marrow-Derived Mesenchymal Stromal Cells to Enhance Engraftment of Cord Blood CD34(+) Transplants.
Cotransplantation of CD34(+) hematopoietic stem and progenitor cells (HSPCs) with mesenchymal stromal cells (MSCs) enhances HSPC engraftment. For these applications, MSCs are mostly obtained from bone marrow (BM). However, MSCs can also be isolated from the Wharton's jelly (WJ) of the human umbilical cord. This source, regarded to be a waste product, enables a relatively low-cost MSC acquisition without any burden to the donor. In this study, we evaluated the ability of WJ MSCs to enhance HSPC engraftment. First, we compared cultured human WJ MSCs with human BM-derived MSCs (BM MSCs) for in vitro marker expression, immunomodulatory capacity, and differentiation into three mesenchymal lineages. Although we confirmed that WJ MSCs have a more restricted differentiation capacity, both WJ MSCs and BM MSCs expressed similar levels of surface markers and exhibited similar immune inhibitory capacities. Most importantly, cotransplantation of either WJ MSCs or BM MSCs with CB CD34(+) cells into NOD SCID mice showed similar enhanced recovery of human platelets and CD45(+) cells in the peripheral blood and a 3-fold higher engraftment in the BM, blood, and spleen 6 weeks after transplantation when compared to transplantation of CD34(+) cells alone. Upon coincubation, both MSC sources increased the expression of adhesion molecules on CD34(+) cells, although stromal cell-derived factor-1 (SDF-1)-induced migration of CD34(+) cells remained unaltered. Interestingly, there was an increase in CFU-GEMM when CB CD34(+) cells were cultured on monolayers of WJ MSCs in the presence of exogenous thrombopoietin, and an increase in BFU-E when BM MSCs replaced WJ MSCs in such cultures. Our results suggest that WJ MSC is likely to be a practical alternative for BM MSC to enhance CB CD34(+) cell engraftment.


Valuable antiviral therapeutic options for the treatment of chronic hepatitis C patients with thrombocytopenia.
Thrombocytopenia in patients with chronic hepatitis C may represent an obstacle for the initiation of antiviral treatment. The aim of this study was to evaluate factors predictive of successful pegylated interferon (PEG-IFN) α2b and ribavirin (RBV) treatment for patients with thrombocytopenia with no history of splenectomy or partial splenic embolization. One hundred and fifty-one chronic hepatitis C patients (genotype 1: n = 110, genotype 2: n = 41) with TCP (<100 × 10(9) /L) at baseline were enrolled. Pretreatment variables included interleukin 28B (IL28B) genotype (rs8099917) and homoeostasis model assessment of insulin resistance score (HOMA-IR). The kinetics of haemoglobin and platelets according to the inosine triphosphatase (ITPA) genotype (rs1127354) were investigated. Sustained virological response (SVR) was significantly more frequent in hepatitis C virus (HCV) genotype 2 (65.9%) than in genotype 1 (34.5%) patients (P < 0.0001). Multiple logistic regression analysis of HCV genotype 1 extracted IL28B TT genotype [odds ratio (OR) 5.97, P = 0.006] and HOMA-IR <2.5 (OR 7.14, P = 0.0016) as significant independent pretreatment predictors of SVR. The analyses of HCV genotype 2 showed that HOMA-IR was significantly related to SVR, but IL28B genotype was not. Patients with ITPA CC genotype showed a significant haemoglobin reduction and lower degree of platelets decrease than those with ITPA CA/AA genotypes. The most common reason for premature discontinuation of treatment was the development of hepatocellular carcinoma (n = 8, 5.3%). In conclusion, HOMA-IR is a useful predictor of SVR for patients with thrombocytopenia infected with HCV genotype 1 or 2 treated with PEG-IFNα2b and RBV. The inclusion of IL28B, ITPA genotypes and HOMA-IR adds valuable therapeutic information.


Costs of promoting exclusive breastfeeding at community level in three sites in South Africa.
Community-based peer support has been shown to be effective in improving exclusive breastfeeding rates in a variety of settings. We conducted a cost analysis of a community cluster randomised-controlled trial (Promise-EBF), aimed at promoting exclusive infant feeding in three sites in South Africa. The costs were considered from the perspective of health service providers. Peer supporters in this trial visited women to support exclusive infant feeding, once antenatally and four times postpartum. The total economic cost of the Promise-EBF intervention was US$393 656, with average costs per woman and per visit of US$228 and US$52, respectively. The average costs per woman and visit in an operational 'non research' scenario were US$137 and US$32 per woman and visit, respectively. Investing in the promotion of exclusive infant feeding requires substantial financial commitment from policy makers. Extending the tasks of multi-skilled community health workers (CHWs) to include promoting exclusive infant feeding is a potential option for reducing these costs. In order to avoid efficiency losses, we recommend that the time requirements for delivering the promotion of exclusive infant feeding are considered when integrating it within the existing activities of CHWs. This paper focuses on interventions for exclusive infant feeding, but its findings more generally illustrate the importance of documenting and quantifying factors that affect the feasibility and sustainability of community-based interventions, which are receiving increased focus in low income settings.


Sequencing and analysis of the Bacillus subtilis lytRABC divergon: a regulatory unit encompassing the structural genes of the N-acetylmuramoyl-L-alanine amidase and its modifier.
The regulatory unit of Bacillus subtilis strain 168 encompassing the structural genes of the N-acetylmuramoyl-L-alanine amidase and of its modifier has been sequenced, and found to be a divergon consisting of divergently transcribed operons lytABC and lytR. Proteins LytA, LytB and LytC are endowed with export signal peptides. Mature LytA is a 9.4 kDa, highly acidic polypeptide whose deduced amino acid sequence points to a lipoprotein. LytB and LytC, the modifier and the amidase, are highly basic. After cleavage of the signal sequence their molecular masses are 74.1 and 49.9 kDa, respectively. These two proteins share considerable homology in their N-terminal moieties and have three GSNRY consensus motifs, characteristic of nearly all amidases. The C-terminal moiety of LytB exhibits homology to the product of spoIID. LytR is a 35 kDa protein which acts as an attenuator of the expression of both lytABC and lytR operons. Transcription of the lytABC operon proceeds from two promoters: PD, identified as P28-7 (Gilman et al., 1984), and an upstream PA. The former only is subject to LytR attenuation. Translational initiation of lytB and lytC is directed by UUG start codons, suggesting that lytA, B and C undergo coupled translation. Transcription of lytR is initiated at two start sites, one of which corresponds to a highly intense PA promoter whereas the other does not seem to share much homology with any of the known promoter consensus sequences. Both promoters are attenuated by LytR. It is confirmed that the synthesis of the amidase is controlled at least in part by SigD, i.e. that it belongs to the fla regulon and that its activity, or part of it, is co-regulated with flagellar motility. The role of the mutations conferring the Sin, Fla and Ifm phenotypes in the expression of the lytABC operon is discussed.


Short-term inhibition of autophagy benefits pancreatic β-cells by augmenting ether lipids and peroxisomal function, and by countering depletion of n-3 polyunsaturated fatty acids after fat-feeding.
Investigations of autophagy in β-cells have usually focused on its homeostatic function. More dynamic roles in inhibiting glucose-stimulated insulin secretion (GSIS), potentially involving remodelling of cellular lipids, have been suggested from in vitro studies but not evaluated in vivo. We employed temporally-regulated deletion of the essential autophagy gene, Atg7, in β-cells. Mice were fed chow or high-fat diets (HFD), in conjunction with deletion of Atg7 for the last 3 weeks (short-term model) or 9 weeks (long-term model). Standard in vivo metabolic phenotyping was undertaken, and 450 lipid species in islets quantified ex vivo using mass spectroscopy (MS). MIN6 cells were also employed for lipidomics and secretory interventions. β-cell function was impaired by inhibiting autophagy in the longer-term, but conversely improved by 3-week deletion of Atg7, specifically under HFD conditions. This was accompanied by augmented GSIS ex vivo. Surprisingly, the HFD had minimal effect on sphingolipid and neutral lipid species, but modulated >100 phospholipids and ether lipids, and markedly shifted the profile of polyunsaturated fatty acid (PUFA) sidechains from n3 to n6 forms. These changes were partially countered by Atg7 deletion, consistent with an accompanying upregulation of the PUFA elongase enzyme, Elovl5. Loss of Atg7 separately augmented plasmalogens and alkyl lipids, in association with increased expression of Lonp2, a peroxisomal chaperone/protease that facilitates maturation of ether lipid synthetic enzymes. Depletion of PUFAs and ether lipids was also observed in MIN6 cells chronically exposed to oleate (more so than palmitate). GSIS was inhibited by knocking down Dhrs7b, which encodes an enzyme of peroxisomal ether lipid synthesis. Conversely, impaired GSIS due to oleate pre-treatment was selectively reverted by Dhrs7b overexpression. A detrimental increase in n6:n3 PUFA ratios in ether lipids and phospholipids is revealed as a major response of β-cells to high-fat feeding. This is partially reversed by short-term inhibition of autophagy, which results in compensatory changes in peroxisomal lipid metabolism. The short-term phenotype is linked to improved GSIS, in contrast to the impairment seen with the longer-term inhibition of autophagy. The balance between these positive and negative inputs could help determine whether β-cells adapt or fail in response to obesity.


Short synthetic endostatin peptides inhibit endothelial migration in vitro and endometriosis in a mouse model.
To determine the active peptide regions inside the angiogenesis inhibitor endostatin that can inhibit endothelial migration in vitro and also inhibit endometriosis in a mouse model. Pharmacologic intervention in a surgically induced mouse model of endometriosis and endothelial migration assay. Animal research and laboratory facility. Eight-week-old, female C57BL/6 mice and human microvascular endothelial cells. Eight overlapping synthetic peptides were tested for inhibitory potential on endothelial migration in vitro. The peptides with significant activity then were given for 4 weeks to mice after implantation of autologous endometrium. Inhibition of vascular endothelial growth factor-induced endothelial migration for in vitro studies. In vivo studies examined the growth rate of endometriotic lesions after 4 weeks of treatment, as well as the effect on estrous cycling and ovulation as assessed by corpus luteum formation. The N-terminal mP-1 peptide and the internal mP-6 peptide inhibited endothelial migration in a dose-dependent manner. Additionally, both synthetic peptides suppressed growth of endometriotic lesions significantly in vivo. However, estrous cycling and corpus luteum formation were normal in both groups. Short endostatin fragments may be promising as a new, nontoxic therapeutic strategy for the treatment of endometriosis without inhibition of normal estrous cycles.


Real-Time Monitoring of Fluorescence in Situ Hybridization Kinetics.
We present a novel method for real-time monitoring and kinetic analysis of fluorescence in situ hybridization (FISH). We implement the method using a vertical microfluidic probe containing a microstructure designed for rapid switching between probe solution and nonfluorescent imaging buffer. The FISH signal is monitored in real time during the imaging buffer wash, during which signal associated with unbound probes is removed. We provide a theoretical description of the method as well as a demonstration of its applicability using a model system of centromeric probes (Cen17). We demonstrate the applicability of the method for characterization of FISH kinetics under conditions of varying probe concentration, destabilizing agent (formamide) content, volume exclusion agent (dextran sulfate) content, and ionic strength. We show that our method can be used to investigate the effect of each of these variables and provide insight into processes affecting in situ hybridization, facilitating the design of new assays.


Image encryption using polarized light encoding and amplitude and phase truncation in the Fresnel domain.
In this paper, an image encryption scheme based on polarized light encoding and a phase-truncation approach in the Fresnel transform domain is proposed. The phase-truncated data obtained by an asymmetric cryptosystem is encrypted and decrypted by using the concept of the Stokes-Mueller formalism. Image encryption based on polarization of light using Stokes-Mueller formalism has the main advantage over Jones vector formalism that it manipulates only intensity information, which is measurable. Thus any intensity information can be encrypted and decrypted using this scheme. The proposed method offers several advantages: (1) a lens-free setup, (2) flexibility in the encryption key design, (3) use of asymmetric keys, and (4) immunity against special attack. We present numerical simulation results for gray-scale and color images in support of the proposed security scheme. The performance measurement parameters relative error and correlation coefficient have been calculated to check the effectiveness of the scheme.


Comparative effects of argon green and krypton red laser photocoagulation for patients with diabetic exudative maculopathy.
Focal treatment of diabetic macular oedema is usually done using a haemoglobin absorbing wave-length, such as argon green laser. This study aimed to compare photocoagulation with argon green (514 nm) and krypton red (647 nm), which is poorly absorbed by haemoglobin, in the focal treatment of patients with diabetic exudative maculopathy. A total of 151 eyes of 78 outpatients were assigned randomly to receive either argon green (n = 79) or krypton red (n = 72) laser treatment. Pretreatment and post-treatment ocular examinations included visual acuity, fundus biomicroscopic examination, and fluorescein angiography. A total of 141 eyes of 73 patients were available for evaluation after 1 year follow up. No statistically significant difference was found between the two treatment groups with respect to visual acuity results, resorption of hard exudates, and resolution of focal retinal oedema. Krypton red laser was effective in the treatment of diabetic exudative maculopathy. Our data suggest that differential absorption of the various wavelengths by haemoglobin within microaneurysms may not be an important factor for ultimate success of focal treatment.


Impact of hospital volume on postoperative complications and in-hospital mortality after musculoskeletal tumor surgery: analysis of a national administrative database.
We are aware of only one report describing the relationship between operative volume and outcomes in musculoskeletal tumor surgery, although numerous studies have described such relationships in other surgical procedures. The aim of the present study was to use a nationally representative inpatient database to evaluate the impact of hospital volume on the rates of postoperative complications and in-hospital mortality after musculoskeletal tumor surgery. We used the Japanese Diagnostic Procedure Combination administrative database to retrospectively identify 4803 patients who had undergone musculoskeletal tumor surgery during 2007 to 2010. Patients were then divided into tertiles of approximately equal size on the basis of the annual hospital volume (number of patients undergoing musculoskeletal tumor surgery): low, twelve or fewer cases/year; medium, thirteen to thirty-one cases/year; and high, thirty-two or more cases/year. Logistic regression analyses were performed to examine the relationships between various factors and the rates of postoperative complications and in-hospital mortality adjusted for all patient demographic characteristics. The overall postoperative complication rate was 7.2% (348 of 4803), and the in-hospital mortality rate was 2.4% (116 of 4803). Postoperative complications included surgical site infections in 132 patients (2.7%), cardiac events in sixty-four (1.3%), respiratory complications in fifty-one (1.1%), sepsis in thirty-one (0.6%), pulmonary emboli in sixteen (0.3%), acute renal failure in eleven (0.2%), and cerebrovascular events in seven (0.1%). The postoperative complication rate was related to the duration of anesthesia (odds ratio [OR] for a duration of more than 240 compared with less than 120 minutes, 2.44; 95% confidence interval [CI], 1.68 to 3.53; p < 0.001) and to hospital volume (OR for high compared with low volume, 0.73; 95% CI, 0.55 to 0.96; p = 0.027). The mortality rate was related to the diagnosis (OR for a metastatic compared with a primary bone tumor, 3.67; 95% CI, 1.66 to 8.09; p = 0.001), type of surgery (OR for amputation compared with soft-tissue tumor resection without prosthetic reconstruction, 3.81; 95% CI, 1.42 to 10.20; p = 0.008), and hospital volume (OR for high compared with low volume, 0.26; 95% CI, 0.14 to 0.50; p < 0.001). We identified an independent effect of hospital volume on outcomes after adjusting for patient demographic characteristics. We recommend regionalization of musculoskeletal tumor surgery to high-volume hospitals in an attempt to improve patient outcomes.


Patient and provider barriers to effective management of gout in general practice: a qualitative study.
To explore patient and provider illness perceptions and barriers to effective management of gout in general practice. A qualitative study involving semistructured face-to-face interviews with patients and health professionals from 25 Nottinghamshire general practices and one central National Health Service hospital. Twenty gout sufferers and 18 health professionals (six general practitioners, five hospital physicians, seven practice nurses). A number of key themes emerged suggesting that several factors impact on patients' access to recommended treatments. The main barriers were patient experiences and lay beliefs of their condition which affected seeking advice and adherence to treatment. There was universal lack of knowledge and understanding of the causes and consequences of gout and that it can be treated effectively by lifestyle change and use of urate lowering therapy (ULT). All participants associated gout with negative stereotypical images portrayed in Victorian cartoons. Many viewed it as self-inflicted or part of ageing and only focused on managing acute attacks rather than treating the underlying cause. The main provider barriers that emerged related to health professionals' lack of knowledge of gout and management guidelines, reflected in the suboptimal information they gave patients and their reluctance to offer ULT as a 'curative' long-term management strategy. There are widespread misconceptions and lack of knowledge among both patients and health professionals concerning the nature of gout and its recommended management, which leads to suboptimal care of the most common inflammatory joint disease and the only one for which we have 'curative' treatment.


Damage and protection cost curves for coastal floods within the 600 largest European cities.
The economic assessment of the impacts of storm surges and sea-level rise in coastal cities requires high-level information on the damage and protection costs associated with varying flood heights. We provide a systematically and consistently calculated dataset of macroscale damage and protection cost curves for the 600 largest European coastal cities opening the perspective for a wide range of applications. Offering the first comprehensive dataset to include the costs of dike protection, we provide the underpinning information to run comparative assessments of costs and benefits of coastal adaptation. Aggregate cost curves for coastal flooding at the city-level are commonly regarded as by-products of impact assessments and are generally not published as a standalone dataset. Hence, our work also aims at initiating a more critical discussion on the availability and derivation of cost curves.


Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan.
This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.


A prospective multicenter study using a new multiband mucosectomy device for endoscopic resection of early neoplasia in Barrett's esophagus.
Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.).


Current COVID-19 treatments: Rapid review of the literature.
As SARS-CoV-2 continues to spread worldwide, it has already resulted in over 110 million cases and 2.5 million deaths. Currently, there are no effective COVID-19 treatments, although numerous studies are under way. SARS-CoV-2, however, is not the first coronavirus to cause serious outbreaks. COVID-19 can be compared with previous human coronavirus diseases, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), to better understand the development of treatments. Databases Medline, Embase and WHO COVID-19 was systematically searched on 9 February 2021 for studies reporting on therapeutic effect of COVID-19 treatments. Clinical trials, case reports, observational studies and systematic reviews in the English language were eligible. 1416 studies were identified and 40 studies were included in this review. Therapies included are: remdesivir, convalescent plasma, hydroxychloroquine, lopinavir/ ritonavir, interferon, corticosteroids, cytokine storm inhibitors and monoclonal antibodies. Remdesivir, convalescent plasma and interferon seems to provide some clinical benefits such as faster recovery time and reduced mortality, but these effects are not clinically significant. Some corticosteroids are effective in reducing mortality in severe COVID-19 patients. Hydroxychloroquine do not convey any beneficial, and therapies such as cytokine storm inhibitors and monoclonal antibodies were also not effective and require further investigation. There is no single therapy effective against COVID-19. However, a combination of therapies administered at different stages of infection may provide some benefit. This conclusion is reflected in the limited effects of these treatments in previous human coronaviruses.


Overexpression of a chromatin architecture-controlling AT-hook protein extends leaf longevity and increases the post-harvest storage life of plants.
Leaf senescence is the final stage of leaf development and is finely regulated via a complex genetic regulatory network incorporating both developmental and environmental factors. In an effort to identify negative regulators of leaf senescence, we screened activation-tagged Arabidopsis lines for mutants that exhibit a delayed leaf senescence phenotype. One of the mutants (ore7-1D) showed a highly significant delay of leaf senescence in the heterozygous state, leading to at least a twofold increase in leaf longevity. The activated gene (ORE7/ESC) encoded a protein with an AT-hook DNA-binding motif; such proteins are known to co-regulate transcription of genes through modification of chromatin architecture. We showed that ORE7/ESC, in addition to binding to a plant AT-rich DNA fragment, could also modify the chromatin architecture, as illustrated by an altered distribution of a histone-GFP fusion protein in the nucleus of the mutant. Globally altered gene expression, shown by microarray analysis, also indicated that activation of ORE7/ESC results in a younger condition in the mutant leaves. We propose that ectopically expressed ORE7/ESC is negatively regulating leaf senescence and suggest that the resulting chromatin alteration may have a role in controlling leaf longevity. Interestingly, activation of ORE7/ESC also led to a highly extended post-harvest storage life.


Discoloration of PMMA, composite, and PEEK.
To assess the discoloration and stain removal potential of different cleaning methods relevant to individual/professional prophylaxis and laboratory cleaning on polyetheretherketone (PEEK), poly(methyl methacrylate) (PMMA)-based, and composite (COMP) materials after storage in different media for 7 days. One thousand three hundred twenty specimens of PEEK, PMMA, and COMP (N = 440 of each group) were prepared and stored in four different media for 7 days to cause stain. Samples were divided into three cleaning groups (n = 10): (i) individual prophylaxis, (ii) laboratory protocols, and (iii) professional prophylaxis. Color was determined by a portable spectrophotometer and calculated between different time points (∆E). The data was statistically evaluated using univariate analyses, Kruskal-Wallis H and Mann-Whitney U tests (p < 0.05). The significantly (p < 0.001) lowest discoloration was found when specimens were stored in distilled water and chlorhexidine (CHX), followed by red wine. Curry solution caused the highest discoloration. PEEK showed the significantly (p < 0.001) lowest color changes, while COMP showed the highest changes. Ultrasonic bath and Air Flow Plus (AFP) were the significantly (p < 0.001) most effective methods to remove staining. The least cleaning effect was found using a soft toothbrush (ST), a medium-hard toothbrush (MT), and SunSparkle (SS) cleaning system. PEEK seems more stable against discolorations than other denture resin materials. Regarding the cleaning potential, individual prophylaxis can be conducted with toothbrushes. For professional prophylaxis, air-abrasion devices using gentle powders are effective. Laboratory protocols should include gentle cleaning methods like ultrasonic bath. Clinicians and dental technicians should inform their patients about the discoloration potential of certain foods/beverages and recommend the most efficient cleaning, but preventive methods.